A variety of cases of both spontaneously occurring human cancers and experimental cancers in animals have been characterized as possessing tumor associated carbohydrate markers. Carbohydrate antigens carrying the Le.sup.x determinant (Gal.beta.1-4[Fuc.alpha.1-3]GlcNAc-) have been found to accumulate in large quantity in human adenocarcinomas. A collection of carbohydrate structures have been determined that have in common the presence of one or more .alpha.1-3 linked fucose residues on GlcNAc, the hallmark of the Le.sup.x determinant structure. Further derivatives of the Le.sup.x structure have been demonstrated. The presence of .alpha.1-3 linked fucose residues on both .alpha.2-3 and .alpha.2-6 terminally sialylated oligosaccharides have given rise to the sialyl-Le.sup.x determinant structure. In addition, .alpha.1-3 fucosylation of blood group H structures have given rise to the Le.sup.y and trifucosyl Le.sup.y determinants.
With the advent of monoclonal antibody technology, a variety of highly specific antibodies have been generated which are directed to many of these related carbohydrate structures. Monoclonal antibodies specific for Le.sup.x and sialyl-Le.sup.x determinant carrying structures have been used for immunostaining tissue sections from normal human fetal and adult tissues as well as human adenocarcinomas. The antibody FH4 (specific for di- or trimeric Le.sup.x determinant) strongly stained a variety of human adenocarcinomas and fetal gastrointestinal and pulmobronchial epithelia during organogenesis. In adult tissues very little staining was observed. Only a small number of normal cells, such as parietal cells of gastric epithelia and Paneth's cells of intestinal mucosa, were positively stained.
Localization and distribution of the sialyl-Le.sup.x antigen has been studied using the sialyl-Le.sup.x determinant specific antibody FH6. These results indicated that a large variety of embryonic and fetal tissues showed positive staining particularly in the epithelial cell layer, however, no staining was observed in various normal adult tissues. Positive staining was also observed in a variety of cancer tissues tested. More recently, the expression of the Le.sup.y antigen has been studied in premalignant and malignant lesions of human colonic epithelium. These results indicated that Le.sup.y was expressed in colorectal adenocarcinomas and in colonic polyps which showed a greater degree of dysplasia. These results indicate that expression of a variety of glycolipids containing internal .alpha.1-3 linked fucose residues on GlcNAc is associated with fetal development and oncogenesis in these tissues and such expression is oncofetal. Another related class of carbohydrate antigens that have been described as tumor-associated contain .alpha.1-4 linked fucose residues on GlcNAc. These are isomeric structures of the Le.sup.x structures in that they differ in the linkage position of the galactose and fucose residues. These structures (Le.sup.a) are part of the Lewis blood group system and are expressed in human cancers in association with the Lewis antigen status of the individual. The most highly studied antigen in this group is an .alpha.2-3 sialylated form of the Le.sup.a antigen. An antibody, CA 19-9, specific for this structure has an apparent specificity for gastrointestinal and pancreatic cancer.
These related antigens expressing .alpha.1-3 or .alpha.1-4 fucose residues are derivatives of a commonly found core carbohydrate structure called the lactoseries. Structures containing .beta.1-3 linked terminal Gal residues and .alpha.1-4 linked fucose residues represent type 1 chain structures while terminal .beta.1-4 Gal residues which can carry .alpha.1-3 linked fucose residues are type 2 chain structures. Study of these antigens have indicated that the expression of both type 1 and type 2 chain based antigens are considered to be oncofetal in human colonic tissues since they are expressed at certain stages of normal development, decrease greatly in adult tissues, and re-appear in association with oncogenesis.
The great diversity of structures that occur in association with oncogenesis based on lacto-series chains along with the serologic diversity of individuals have so far prevented the finding of a single antibody which could recognize with great fidelity a premalignant or malignant condition necessary for diagnostic screening. This has limited the potential of the use of these carbohydrate structures in defining the disease status. The presence of a complex diversity of related structures in premalignant and malignant tissues tend to obscure the specific biochemical event that is responsible for their synthesis. Identification and exploitation of the specific lesion responsible for expression of both type 1 and 2 lacto-series chain structures could give rise to a general and sensitive process for survey of the disease status of any individual irrespective of their serological status. This would represent obvious improvements in the use of carbohydrate structures as sentinals for early stages in oncogenesis. The discoveries herein show results which indicate an alteration common to all colonic adenocarcinomas responsible for the formation of this complex series of carbohydrate antigens. This forms the basis of a method for diagnostic or prognostic screening of individuals which would represent a significant improvement over current technology.